SURVIVAL OF MOUSE PANCREATIC-ISLET ALLOGRAFTS IN RECIPIENTS TREATED WITH ALLOGENEIC SMALL LYMPHOCYTES AND ANTIBODY TO CD40 LIGAND

Combined treatment with allogeneic small lymphocytes or T-depleted sma ll lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitt ed indefinite pancreatic islet allograft survival in 37 of 40 recipien ts that differed from islet donors at major and minor histocompatibili ty loci. The effect of the allogeneic small lymphocytes was donor anti gen-specific. Neither treatment alone was as effective as combined tre atment, although anti-CD40L by itself allowed indefinite islet allogra ft survival in 40% of recipients. Our interpretation is that small lym phocytes expressing donor antigens in the absence of appropriate costi mulatory signals are tolerogenic for alloreactive host cells. Anti-CD4 0L antibody may prevent host T cells from inducing costimulatory signa ls in donor lymphocytes or islet grafts.